US11938484B2 - Uniform fluid film cooling device - Google Patents
Uniform fluid film cooling device Download PDFInfo
- Publication number
- US11938484B2 US11938484B2 US17/244,419 US202117244419A US11938484B2 US 11938484 B2 US11938484 B2 US 11938484B2 US 202117244419 A US202117244419 A US 202117244419A US 11938484 B2 US11938484 B2 US 11938484B2
- Authority
- US
- United States
- Prior art keywords
- substrate
- temperature
- cooling
- heating element
- thermal
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active, expires
Links
- 239000012530 fluid Substances 0.000 title claims abstract description 66
- 238000001816 cooling Methods 0.000 title abstract description 51
- 238000010438 heat treatment Methods 0.000 claims abstract description 57
- 239000000758 substrate Substances 0.000 claims description 65
- 238000006243 chemical reaction Methods 0.000 claims description 14
- 238000011144 upstream manufacturing Methods 0.000 claims description 13
- 238000004891 communication Methods 0.000 claims description 7
- 238000000034 method Methods 0.000 abstract description 37
- 238000005382 thermal cycling Methods 0.000 abstract description 22
- 239000003570 air Substances 0.000 description 17
- 108020004414 DNA Proteins 0.000 description 16
- 102000053602 DNA Human genes 0.000 description 16
- 239000010408 film Substances 0.000 description 12
- 238000003752 polymerase chain reaction Methods 0.000 description 12
- 230000003321 amplification Effects 0.000 description 6
- 238000003199 nucleic acid amplification method Methods 0.000 description 6
- 150000007523 nucleic acids Chemical class 0.000 description 6
- 239000000523 sample Substances 0.000 description 6
- 108020004682 Single-Stranded DNA Proteins 0.000 description 5
- 238000000137 annealing Methods 0.000 description 5
- 102000039446 nucleic acids Human genes 0.000 description 5
- 108020004707 nucleic acids Proteins 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000008901 benefit Effects 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 239000012080 ambient air Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000001351 cycling effect Effects 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 239000012212 insulator Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000010409 thin film Substances 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 238000004026 adhesive bonding Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- 238000009529 body temperature measurement Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000002826 coolant Substances 0.000 description 1
- 239000012809 cooling fluid Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000003116 impacting effect Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000003331 infrared imaging Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000006903 response to temperature Effects 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 230000002311 subsequent effect Effects 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F28—HEAT EXCHANGE IN GENERAL
- F28D—HEAT-EXCHANGE APPARATUS, NOT PROVIDED FOR IN ANOTHER SUBCLASS, IN WHICH THE HEAT-EXCHANGE MEDIA DO NOT COME INTO DIRECT CONTACT
- F28D1/00—Heat-exchange apparatus having stationary conduit assemblies for one heat-exchange medium only, the media being in contact with different sides of the conduit wall, in which the other heat-exchange medium is a large body of fluid, e.g. domestic or motor car radiators
- F28D1/02—Heat-exchange apparatus having stationary conduit assemblies for one heat-exchange medium only, the media being in contact with different sides of the conduit wall, in which the other heat-exchange medium is a large body of fluid, e.g. domestic or motor car radiators with heat-exchange conduits immersed in the body of fluid
- F28D1/03—Heat-exchange apparatus having stationary conduit assemblies for one heat-exchange medium only, the media being in contact with different sides of the conduit wall, in which the other heat-exchange medium is a large body of fluid, e.g. domestic or motor car radiators with heat-exchange conduits immersed in the body of fluid with plate-like or laminated conduits
- F28D1/0366—Heat-exchange apparatus having stationary conduit assemblies for one heat-exchange medium only, the media being in contact with different sides of the conduit wall, in which the other heat-exchange medium is a large body of fluid, e.g. domestic or motor car radiators with heat-exchange conduits immersed in the body of fluid with plate-like or laminated conduits the conduits being formed by spaced plates with inserted elements
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L7/00—Heating or cooling apparatus; Heat insulating devices
- B01L7/52—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6844—Nucleic acid amplification reactions
- C12Q1/6846—Common amplification features
-
- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F28—HEAT EXCHANGE IN GENERAL
- F28C—HEAT-EXCHANGE APPARATUS, NOT PROVIDED FOR IN ANOTHER SUBCLASS, IN WHICH THE HEAT-EXCHANGE MEDIA COME INTO DIRECT CONTACT WITHOUT CHEMICAL INTERACTION
- F28C3/00—Other direct-contact heat-exchange apparatus
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/18—Means for temperature control
- B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/18—Means for temperature control
- B01L2300/1838—Means for temperature control using fluid heat transfer medium
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/18—Means for temperature control
- B01L2300/1894—Cooling means; Cryo cooling
-
- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F28—HEAT EXCHANGE IN GENERAL
- F28D—HEAT-EXCHANGE APPARATUS, NOT PROVIDED FOR IN ANOTHER SUBCLASS, IN WHICH THE HEAT-EXCHANGE MEDIA DO NOT COME INTO DIRECT CONTACT
- F28D21/00—Heat-exchange apparatus not covered by any of the groups F28D1/00 - F28D20/00
- F28D2021/0019—Other heat exchangers for particular applications; Heat exchange systems not otherwise provided for
- F28D2021/0022—Other heat exchangers for particular applications; Heat exchange systems not otherwise provided for for chemical reactors
-
- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F28—HEAT EXCHANGE IN GENERAL
- F28D—HEAT-EXCHANGE APPARATUS, NOT PROVIDED FOR IN ANOTHER SUBCLASS, IN WHICH THE HEAT-EXCHANGE MEDIA DO NOT COME INTO DIRECT CONTACT
- F28D21/00—Heat-exchange apparatus not covered by any of the groups F28D1/00 - F28D20/00
- F28D2021/0019—Other heat exchangers for particular applications; Heat exchange systems not otherwise provided for
- F28D2021/005—Other heat exchangers for particular applications; Heat exchange systems not otherwise provided for for medical applications
Definitions
- the present disclosure relates to non-contact devices and methods for cooling thermal cycling systems, including in systems for reactions such as the polymerase chain reaction.
- PCR Polymerase chain reaction
- DNA deoxyribonucleic acid
- PCR phases of denaturing, annealing, and extension occur at different temperatures and cause target DNA molecule samples to replicate themselves. Temperature cycling (thermal cycling) requirements vary with particular nucleic acid samples and assays.
- dsDNA double stranded DNA
- ssDNA single stranded DNA
- primers are attached to the single stranded DNA molecules.
- Single stranded DNA molecules form double stranded DNA in the extension phase through specific bindings between nucleotides in the PCR solution and the single stranded DNA.
- Typical temperatures for PCR are 95° C. for denaturing, 55° C. for annealing, and 72° C. for extension.
- the temperature is held at each phase for a certain amount of time which may be a fraction of a second up to a few tens of seconds.
- the DNA is doubled at each cycle, and it typically takes 20 to 40 cycles to produce enough DNA for certain applications.
- the sample temperatures at the different phases must be accurately controlled.
- High throughput approaches to performing PCR and other amplification reactions have are common and may involve amplification reactions in microfluidic devices, as well as methods for detecting and analyzing amplified nucleic acids in or on the devices.
- Cooling mechanisms present in thermal cycling systems (including microfluidic systems) used for PCR and other thermal cycling reactions rely on multiple methods in order to provide both the speed in switching between temperatures and the uniformity of temperature required for successful reactions.
- the majority of these systems utilize heating and cooling mechanisms that are based on physical contact of the substrate or sample in question via a heat sink or thermoelectric device.
- the nature of this type of connection leads to an increase in the thermal mass of the system, which in turn also increases the heater power required to compensate accordingly.
- non-contact methods such as forced fluid convection can cool very rapidly but typically are not very uniform in temperature unless the fluid has been heated to the target temperature. In order to maintain the flow rate required for a given rate of cooling, the power needed to heat the entire cooling fluid to the target temperature can be larger than desired and/or not feasible.
- cooling speed and thermal gradient in the area of interest are critical physical characteristics to the functioning of the device. It is ideal to have the thermal gradient within a very small temperature range so the entire solution is heated evenly and the PCR reactions occur at the same time and rate everywhere in the reaction chamber. Cooling can be accomplished in many traditional ways, from using a heat sink to a Thermoelectric device. However, these methods are based on physical contact, which is subject to variations in surface contact quality that can introduce additional complications to a system.
- An alternate, non-contact method can be to use a cooling medium such as a gas or liquid to carry heat away from the surface via forced convective cooling.
- a cooling medium such as a gas or liquid
- forced convection can result in local temperature gradients across the surface of the chip due to stagnation of impinging jets or the inherent thermal boundary layer formation when fluid flows parallel across the surface.
- heating of the bulk fluid to the end point or goal temperature before flowing it over the surface can help to prevent thermal overshoot of the desired temperature.
- the present disclosure relates to a device and method for regulating heating and cooling of a substrate in a thermal cycling system using a thermal boundary layer.
- a fluidic device comprising a substrate, wherein the substrate comprises at least one reaction chamber; a first heating element; and, a second heating element; means for providing a fluid flow that is flowed along one side of the substrate providing a thin fluid film; wherein the thin fluid film is in thermal communication with the substrate; wherein the first heating element applies heat to the substrate, and, wherein the second heating element is in thermal communication with the thin fluid film.
- the second heating element is incorporated in the fluid flow upstream of the first heating element.
- the second heating element can be located on the same side of the substrate as the thin fluid film.
- the thin fluid film comprises a thermal boundary layer adjacent to a surface of the substrate. In one aspect, increasing the temperature of the fluid regulates the cooling of the substrate.
- a fourth aspect there is provided method for cooling a substrate, comprising the steps of: (i) heating a substrate by turning on a primary heating element, which primary heating element is turned off when the substrate is heated to the desired temperature; and (ii) causing a fluid having a lower temperature than the substrate to flow over at least one surface of the substrate, causing a thermal boundary layer to form.
- the thermal boundary layer can cause the substrate to cool rapidly.
- the method can additionally comprises the steps of (iii) providing a secondary heating element located upstream of the substrate; (iv) causing the secondary heating element to heat the fluid flowing over the substrate such that the temperature of the thermal boundary layer is increased, and (v) turning off the secondary heating element after the desired substrate temperature is reached.
- the method steps can be repeated sequentially in order to provide thermal cycling of the substrate. Thermal cycling can occur until amplification of a nucleic acid sample occurs.
- FIG. 1 is an exploded view of an exemplary device including a cartridge holder and a cooling stream directed at a microfluidic cartridge within the cartridge holder.
- FIG. 2 is a cross sectional view of the exemplary device of FIG. 1 .
- FIG. 3 is a depiction of the formation of the thermal boundary layer in the bulk fluid flow stream directed at a microfluidic cartridge within the cartridge holder.
- FIG. 4 is a uniformity profile showing temperature uniformity across five chip chambers during testing.
- FIG. 5 is a cooling speed plot of fluid temperature vs. time.
- FIG. 6 is a plot of an exemplary thermal cycling sequence depicting temperature vs time.
- the present disclosure is directed to methods and devices that will minimize undesirable thermal gradients in devices that perform PCR or other thermal cycling reactions, while also lowering power consumption, increasing the cooling speed and decreasing the size of the device.
- the present disclosure provides a device and method wherein a preheating element is located upstream of the substrate or cartridge on which the thermal cycling assay will be run, such that the preheating element heats a thin fluid film near the cartridge, known as a thermal boundary layer, to the desired temperature, rather than heating the entire fluid flow stream.
- FIG. 1 (exploded view) and FIG. 2 (cross section) provide an exemplary representation of a device of the present disclosure, which has been designed to suspend a microfluidic cartridge 3 in a holder (top half 1 and bottom half 2 ) such that fluid flow can be blown across one side of the cartridge.
- Microfluidic cartridge 3 has an upper side and a lower side.
- the top half of the cartridge holder structure 1 has an upper side and a lower side
- the bottom half of the cartridge holder structure additionally has an upper side and a lower side.
- Microfluidic cartridge 3 is placed between the top half of cartridge holder 1 and the bottom half of cartridge holder 2 , such that the upper side of microfluidic cartridge 3 engages with the lower side of the top half of the cartridge holder structure 1 , and the lower side of microfluidic cartridge 3 engages with the upper side of the bottom half of the cartridge holder structure 3 .
- Top half of cartridge holder 1 and bottom half of cartridge holder 2 are secured together around the cartridge 3 using fixation hardware 6 .
- fixation hardware 6 When fixed together, top half of cartridge holder 1 and bottom half of cartridge holder 2 together form cartridge holder 8 .
- Cartridge holder 8 may include viewing window 7 which enables imaging of the microfluidic cartridge 3 while in the cartridge holder 8 .
- Cartridge holder 8 can be mounted on or within a microfluidic device or system, including a bench top system, utilizing cartridge holder mount 9 .
- the mounting of cartridge holder 8 allows the cartridge 3 to “float” in space, such that a fluid flow can be directed across one side of cartridge 3 .
- the fluid flow comprises air or another gas.
- a blower, fan or the like can be attached to the cooling air inlet duct 5 .
- the blower, fan or the like can be operated by a controller, which can operate the fan in response to temperature readings, desired temperatures of the substrate or microfluidic cartridge, or in response to a desired thermal cycle.
- the fluid flow can be a liquid.
- Heating element 4 (also referred to as a preheating element) is located upstream of the cartridge 3 .
- Cooling air inlet duct 5 is located further upstream from the heating element 4 , such that the heating element 4 and the cooling air inlet duct 5 are configured such that the bulk fluid flow form the cooling air inlet duct 5 is in thermal communication with heater 4 , such that heat is directed into at least a portion of the bulk fluid flow stream that is directed across one side of cartridge 3 by cooling air inlet duct 5 . While FIG. 1 and FIG. 2 depict that the fluid flow is directed across the lower side of cartridge 3 , alternate configurations can be provided which would direct the fluid flow along a different side, for instance, the upper side of cartridge 3 .
- the exemplary structures within the fluid chamber surrounding the cartridge holder 8 and the microfluidic cartridge 3 , there may be structures such as walls, baffles, and similar in order to direct the flow and maintain the flow speed across the substrate to direct the flow and maintain the flow speed across the substrate. These structures may or may not be optically transparent for imaging of the microfluidic cartridge. Modifications can be made to the exemplary structures provided herein that are within the scope of this disclosure provided enables the formation of a thermal boundary layer at the boundary of a bulk fluid flow that is supplied heat via an upstream heater and which thermal boundary layer is in thermal communication with the microfluidic cartridge or substrate, thereby allowing rapid and uniform heating and cooling of the microfluidic cartridge or substrate.
- the device will additionally comprise one or more temperature measuring devices (i.e., temperature probes) which can be located throughout the device, including, but not limited to in the cooling air inlet duct 5 , at the heater 4 , on or in the substrate or microfluidic cartridge 3 , or in other advantageous positions to obtain temperature measurements that can be used to determine or estimate the temperature of the thermal boundary layer.
- the temperature measuring devices may be, for example, wire-like with a probe tip suspended in air.
- the wire may be supported by, for example, gluing or press-fitting the wire to a side of the device.
- Other temperature measuring device may be used, such as, for example, sensors in plastic or glass beads or other standard electronic packages.
- the temperature measuring devices may all be of the same types or of different types.
- the temperature measuring device may be any suitable device known in the art for measuring temperature.
- the temperature measuring device may be, for example, a thermistor, thermocouple or resistance temperature detector.
- one or more thermal controllers may be used to control the upstream preheating element 4 and the main heater which drives the temperature dependent reactions on the microfluidic device.
- a single controller may control both heaters, or each heater can be controlled by a separate controller.
- the one or more controllers can cause the temperature of the upstream preheating element 4 or the main heater to increase or decrease the temperature according to a measured temperature within the device, a desired temperature of the substrate or microfluidic cartridge 3 , desired thermal cycling conditions, or any combination thereof.
- a controller can operate a blower or fan to cause the cooling air inlet duct to provide a bulk fluid flow towards the preheating element 4 and the substrate or microfluidic cartridge 3 , such that when the preheating element 4 is turned on, a thermal boundary layer is formed.
- FIG. 3 shows a cross sectional view of the device of FIGS. 1 and 2 with the theoretical fluid flow regions displayed, including a representation of the thermal boundary layer 40 formation.
- the cooling air inlet duct 5 (not depicted in FIG. 3 ) directs a bulk fluid flow 30 across a surface of the heating element 4 located and the microfluidic cartridge 3 .
- the bulk fluid flow 30 blowing across the heating element 4 , which causes a portion of the bulk fluid flow 30 at the interface or border between the bulk fluid flow and the lower surfaces of the heater 4 and microfluidic chip 3 to be in thermal communication with the heating element 4 .
- This heating of the border area of the bulk fluid flow 30 generates a thermal boundary layer 40 (hatched in FIG. 3 ).
- the fluid film temperature (T film ) 140 in the thermal boundary layer 40 can be approximated by an average of the preheating element 4 surface temperature (T preheater ) 104 and the bulk fluid 30 temperature (T fluid ) 130 .
- the heating of the fluid film or thermal boundary layer 40 allows for the microfluidic chip 3 temperature (T cartridge ) 103 to acclimate to that of the fluid film temperature of the thermal boundary layer to prevent thermal overshoot or undershoot of the target temperature.
- the small heater 4 and thermal boundary layer 40 thermal mass allows for rapid changes of the fluid temperature, allowing cooler air for rapid cooling rates and then rapidly heating the thermal boundary layer 40 for a more insulating effect, thereby minimizing thermal overshoot of the target substrate.
- Heating in this manner allows for accurate temperature control to be maintained via the thermal boundary layer 40 fluid film temperature, which requires significantly less power to preheat, allowing for faster temperature changes within the thermal boundary layer for more effective cooling without the need for a large heating element for the entire bulk fluid flow.
- heater 4 is not directly responsible for the thermal cycling of the microfluidic cartridge 3 . Rather, the thermal cycling device or system will include a second heater (“main heater”) that is the primary heating source for the substrate or microfluidic cartridge 3 and that the upstream preheating element 4 is primarily used during the cooling phase of thermal cycling.
- the present disclosure provides a method for cooling a substrate, wherein the substrate can be a microfluidic cartridge or other reagent container.
- the method comprises the steps of (i) heating a substrate by turning on a primary heating element, until such time as the substrate is heated to the desired temperature, at which time the primary heating element is turned off; and (ii) causing a fluid flow having a lower temperature than that of the substrate to flow over a surface of the substrate, causing a thermal boundary layer 40 to form, wherein the thermal boundary layer has a different temperature than that of the fluid flow.
- Such method allows for the rapid cooling of the substrate or microfluidic cartridge, and the method may additional comprise step (iii) providing a secondary heating element (preheating element) 4 located upstream of the substrate.
- the primary heating element and secondary heating element (preheating element) 4 can be controlled by one or more thermal controllers.
- the method of cooling a substrate can additionally comprise the step of (iv) causing the secondary heating element to heat the fluid flowing over the substrate such that the temperature of the thermal boundary layer is increased. In some embodiments, the warming of the fluid regulates the cooling of the substrate.
- the method can also additionally comprising the step of (v) turning off the secondary heating element after the desired substrate temperature is reached. Steps (i) to (v) can be caused to occur to occur repeatedly to provide thermal cycling of the substrate, and the thermal cycling can be repeated until amplification of a nucleic acid sample occurs.
- FIG. 6 shows an exemplary diagram of a thermal cycling sequence for a device according to the present disclosure.
- Arrows show key points in the cycle where the fan is turned on for cooling, and after a set amount of time the upstream preheating element 4 is turned on.
- the device can take advantage of the rapid cooling using ambient or cooled air during the initial cooling stages, then after nearing the lower target temperature, the preheating element can be turned on to prevent thermal under/overshoot and maintain the critical annealing temperature uniformity.
- the power requirements are lowered significantly compared to heating the entire fluid before passing it over the chip.
- the method and device described herein maintains accurate temperature control of the substrate or microfluidic cartridge via the fluid film temperature, preventing thermal overshoot or undershoot of the substrate or microfluidic cartridge from occurring as the difference between the temperature of the substrate or microfluidic chip and the desired temperature narrows.
- the method and device described herein can increase the cooling speed by using a faster fluid flow, but because the entire bulk fluid flow 30 does not have to be heated (as only the thermal boundary layer 40 is heated), the power requirements are not increased significantly.
- a thermal boundary layer 40 created by heating a bulk fluid flow 30 with a preheating element 4 can be used both for cooling a substrate or microfluidic cartridge as well as for heating a substrate or microfluidic cartridge during a thermal cycling reaction.
- the thermal boundary layer can be heated to a temperature in between the current temperature of the substrate or microfluidic cartridge and the desired temperature to more rapidly raise the temperature of the substrate or cartridge before acting as an insulator to prevent an overshooting of the desired temperature.
- the thermal boundary layer can be heated to a temperature over the desired temperature to begin rapidly raising the temperature of the substrate or cartridge before the preheating element 4 is turned off or the temperature is reduced to allow the thermal boundary layer to again act as an insulator to prevent an overshooting of the desired temperature.
- the present disclosure relates to the heating and cooling of a substrate or microfluidic cartridge for thermal cycling applications, therefore, although the description and figures herein primarily relate to the heating and cooling mechanisms, it is intended that the disclosed device and method are integrated into or used with a thermal cycling device, system or method.
- the device and method of the present disclosure can be utilized with or incorporated into known thermal cycling devices, systems or methods, including, for instance, those described in any of US20200232020, WO2020154407, U.S. Ser. No. 10/226,772, U.S. Pat. Nos. 9,919,314, 9,829,389, 9,823,135, 9,554,422, and, U.S. Pat. No. 9,542,526 the contents of which are hereby incorporated herein in their entirety.
- Feasibility tests were performed where four separate conditions were tested wherein air was used as the working fluid, which was transported over the substrate via a duct system connected to an external blower. During the feasibility tests, an optical heating method was used as the main heater of the substrate, and then various conditions of cooling with and without the pre-heating element were tested to see the subsequent effects, both on cooling speed and uniformity between the fluidic chambers.
- the chip used for the tests was made of a polymer material and was supplied with five separate chambers filled with deionized water, such that each one could be compared against the other for uniformity via infrared imaging. Four separate test conditions were utilized:
- FIG. 4 is a uniformity profile across the five separate chambers present on the substrate. Each hump of the curve represents the fluid in one of the five chambers.
- the chart corresponds to the bulk fluid flow (airflow) from right to left, i.e., the chamber depicted on the first right side of the plot was at the leading edge in the airflow stream.
- the chart and the depicted chamber to chamber temperature ranges the smallest temperature variation between chambers occurred when both the main heater and the preheating element were used, thereby generating a thermal boundary layer in the airflow.
- FIG. 5 additionally shows that uniformity was improved substantially when using the preheating method versus other methods.
- the cooling speed was not significantly affected by the preheating. This can be explained by the lag time when turning the heater on.
- the preheating element takes some time to heat up, and during this process cool air is flowing over the chip and cooling it rapidly. After several seconds, the preheating element reaches the target temperature and the preheated air acts to insulate and maintain the uniform cartridge temperatures seen.
- a cooling rate of 8° C./s and uniformity of ⁇ 1.2° C. was achieved with the device of the present disclosure.
- spatially relative terms such as “under” “beneath”, “below”, “lower”, “above”, “upper”, “proximal”, “distal”, and the like, can be used herein for ease of description to describe one element or feature's relationship to another element(s) or feature(s) as illustrated in the various figures. It should be understood, however, that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if the device in the figures is turned over, elements described as “below” or “beneath” other elements or features would then be oriented “above” the other elements or features. Thus, a relative spatial term such as “below” can encompass both an orientation of above and below.
- the device can be otherwise oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein are to be interpreted accordingly. Similarly, the relative spatial terms “proximal” and “distal” can also be interchangeable, where applicable.
- the term “about,” as used herein means, for example, within 10%, within 5%, or less. In some embodiments, the term “about” can mean within measurement error.
- first, second, third, etc. can be used herein to describe various elements, components, regions, parts and/or sections. It should be understood that these elements, components, regions, parts and/or sections should not be limited by these terms. These terms have been used only to distinguish one element, component, region, part, or section from another region, part, or section. Thus, a first element, component, region, part, or section discussed below could be termed a second element, component, region, part, or section without departing from the teachings herein.
Landscapes
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- General Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Clinical Laboratory Science (AREA)
- Physics & Mathematics (AREA)
- Mechanical Engineering (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Analytical Chemistry (AREA)
- Biotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Thermal Sciences (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
Abstract
Description
-
- (1) ambient air cooling (main heater off, preheating element off);
- (2) preheated air cooling (main heater off, preheating element on)
- (3) ambient air cooling plus optical heating of the microfluidic chip, (main heater on, preheating element off) and
- (4) preheated air cooling plus optical heating of the microfluidic chip (main heater on, preheating element on).
Claims (4)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US17/244,419 US11938484B2 (en) | 2020-04-30 | 2021-04-29 | Uniform fluid film cooling device |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US202063018004P | 2020-04-30 | 2020-04-30 | |
US17/244,419 US11938484B2 (en) | 2020-04-30 | 2021-04-29 | Uniform fluid film cooling device |
Publications (2)
Publication Number | Publication Date |
---|---|
US20210339257A1 US20210339257A1 (en) | 2021-11-04 |
US11938484B2 true US11938484B2 (en) | 2024-03-26 |
Family
ID=78292388
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US17/244,419 Active 2042-01-23 US11938484B2 (en) | 2020-04-30 | 2021-04-29 | Uniform fluid film cooling device |
Country Status (1)
Country | Link |
---|---|
US (1) | US11938484B2 (en) |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5066377A (en) * | 1986-07-04 | 1991-11-19 | Diagen Institute fur molekularbiologische Diagnostik GmbH | Method and device for producing a controllable and reproducible temperature gradient and use thereof |
US6425438B1 (en) * | 2000-06-13 | 2002-07-30 | Dan-Kar Corporation | Method for defrosting a container and a frozen liquid therein |
US20070281304A1 (en) * | 2006-06-05 | 2007-12-06 | The Regents Of The University Of Michigan | Liquid flow actuation and suspension manipulation using surface tension gradients |
US20100112567A1 (en) * | 2006-11-03 | 2010-05-06 | Siemens Healthcare Diagnostics Inc. | Random access system and method for polymerase chain reaction testing |
US20110152108A1 (en) * | 2008-03-06 | 2011-06-23 | Brenan Colin J H | Devices and Methods for Thermally-Mediated Chemical Reactions |
US8012765B2 (en) * | 1998-08-21 | 2011-09-06 | Agilent Technologies, Inc. | Method for mixing a film of fluid |
US20120052560A1 (en) * | 2010-08-31 | 2012-03-01 | Canon U.S. Life Sciences, Inc. | System and method for serial processing of multiple nucleic acid assays |
-
2021
- 2021-04-29 US US17/244,419 patent/US11938484B2/en active Active
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5066377A (en) * | 1986-07-04 | 1991-11-19 | Diagen Institute fur molekularbiologische Diagnostik GmbH | Method and device for producing a controllable and reproducible temperature gradient and use thereof |
US8012765B2 (en) * | 1998-08-21 | 2011-09-06 | Agilent Technologies, Inc. | Method for mixing a film of fluid |
US6425438B1 (en) * | 2000-06-13 | 2002-07-30 | Dan-Kar Corporation | Method for defrosting a container and a frozen liquid therein |
US20070281304A1 (en) * | 2006-06-05 | 2007-12-06 | The Regents Of The University Of Michigan | Liquid flow actuation and suspension manipulation using surface tension gradients |
US20100112567A1 (en) * | 2006-11-03 | 2010-05-06 | Siemens Healthcare Diagnostics Inc. | Random access system and method for polymerase chain reaction testing |
US20110152108A1 (en) * | 2008-03-06 | 2011-06-23 | Brenan Colin J H | Devices and Methods for Thermally-Mediated Chemical Reactions |
US20120052560A1 (en) * | 2010-08-31 | 2012-03-01 | Canon U.S. Life Sciences, Inc. | System and method for serial processing of multiple nucleic acid assays |
Also Published As
Publication number | Publication date |
---|---|
US20210339257A1 (en) | 2021-11-04 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7346503B2 (en) | Systems, methods and devices for automated incubation | |
US9266109B2 (en) | Thermal control system and method for chemical and biochemical reactions | |
AU746098B2 (en) | Microfluidic system with electrofluidic and electrothermal controls | |
KR101203402B1 (en) | System and method for heating, cooling and heat cycling on microfluidic device | |
US9221056B2 (en) | Microfluidic devices with integrated resistive heater electrodes including systems and methods for controlling and measuring the temperatures of such heater electrodes | |
US20180178218A1 (en) | Heat flow polymerase chain reaction systems and methods | |
JP2009526549A (en) | Biological or chemical sample temperature control device and method of use thereof | |
WO2014115863A1 (en) | Nucleic acid amplifying device and method for detecting abnormal temperature regulating function | |
JP6159252B2 (en) | Thermal calibration | |
US11123739B2 (en) | Thermal cycling methods and apparatuses for carrying out efficient polymerase chain reaction (PCR) processes to amplify deoxyribonucleic acid (DNA) | |
JP4564924B2 (en) | Biological sample analyzer | |
EP3502276B1 (en) | Convective pcr device | |
US20220001387A1 (en) | Thermal cycling methods and apparatuses for carrying out efficient polymerase chain reaction (pcr) processes to amplify deoxyribonucleic acid (dna) | |
US11938484B2 (en) | Uniform fluid film cooling device | |
Kim et al. | PID temperature control system-based microfluidic PCR chip for genetic analysis | |
KR20190054212A (en) | Amplification Apparatus and Method of DNA | |
WO2009032087A1 (en) | Microfluidic devices with integrated resistive heater electrodes | |
US9766139B2 (en) | Compound calibrator for thermal sensors | |
WO2024144598A1 (en) | Method of developing heat control platform for isothermal nucleic acid amplification techniques | |
Fung et al. | Liquid crystal thermography of an on-chip polymerase chain reaction micro-thermocycler | |
KR20090055201A (en) | Pcr device and pcr method using marangoni convection and electro-capillary flow | |
Ji et al. | ON-CHIP MELTING CURVE ANALYSIS WITH A PRECISE TEMPERATURE COMPENSATION METHOD | |
Barrett et al. | Thermal analysis of a novel continuous flow multi layered polymerase chain reaction device |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
FEPP | Fee payment procedure |
Free format text: ENTITY STATUS SET TO UNDISCOUNTED (ORIGINAL EVENT CODE: BIG.); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: DOCKETED NEW CASE - READY FOR EXAMINATION |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: NON FINAL ACTION MAILED |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: RESPONSE TO NON-FINAL OFFICE ACTION ENTERED AND FORWARDED TO EXAMINER |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: NOTICE OF ALLOWANCE MAILED -- APPLICATION RECEIVED IN OFFICE OF PUBLICATIONS |
|
AS | Assignment |
Owner name: CANON VIRGINIA, INC., VIRGINIA Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:HENSLEY, MAXWELL;REEL/FRAME:066393/0435 Effective date: 20240206 |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: PUBLICATIONS -- ISSUE FEE PAYMENT VERIFIED |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: PUBLICATIONS -- ISSUE FEE PAYMENT VERIFIED |
|
STCF | Information on status: patent grant |
Free format text: PATENTED CASE |